Cancer Flashcards
(26 cards)
What are carcinomas?
Cancers derived from epithelial cells
Accounts for 80% of all tumours
2 main types of carcinoma
Most tumours arise from epithelial cells
- Squamous cell carcinomas = tumours arising from epithelial cells that form protective layers
- Adenomas (benign)/ Adenocarcinomas = tumours arising from secretory epithelial cells
Time frame of human cancers
Develop over decades
What is a benign tumour?
Early/intermediate/late adenomas
What is a malignant tumour?
A carcinoma
Where does colon cancer metastasise?
In the liver
Where does breast cancer metastasise?
In the brain
Hallmarks of cancer
- Sustaining proliferative signalling
- Evading cell growth
- Genome instability & mutation
- Resisting cell death
How do cancer cells acquire hallmarks?
- Cancer cell manifests as deregulated tissue homeostasis
- Is inherently a genetic disease
- Caused by mutations in oncogenes and tumour suppressor genes
- Leading to abnormal cell behaviour
- In turn, disrupting normal tissue architecture
Oncogenes and TSG control proliferation, differentiation and survival of cells
How do mutations disrupt tissue homeostasis?
Mutated genes alter gene expression profiles and cause dysfunctional protein networks
= abnormal cell function and loss of tissue homeostasis
Human genetics
Diploid organisms with 2 copies of every chromosome = 2 copies of every gene
Viral oncogenes
- retroviruses have RNA genomes that are converted to DNA by reverse transcription
- DNA then integrates into a host chromosome so that viral genomes can be synthesised
- RSV had an extra gene called v-src
- v-src was the first oncogene to be discovered
What is src?
A non-receptor tyrosine kinase
Role of Ras-GTPase
Frequently mutated in variety of cancer types
Only a single mutated Ras allele is required
Mutation causes Ras to be locked in the active form even when mitogens aren’t present
Examples of oncogenic mutations
- Ras Beta-catenin = mutation in the coding sequence causes hyperactive protein made in normal amounts
- MYC ERB2 = gene amplification causes normal protein to be overproduced
- Bcl-2 = chromosome rearrangement causes nearby regulatory DNA sequence to overproduce normal protein
- Bcr-Abl = chromosome rearrangement causes fusion to actively transcribed gene to produce hyperactive fusion protein
What are sporadic tumour suppressor genes?
No family history
Low risk of other tumours
What are familial tumour suppressor genes?
Family history
High risks of other tumours
Rb and the regulation of the cell cycle
Rb typically inhibits the E2F transcription factor
In the absence of Rb function (when mutated), E2F is constitutively active and will drive entry into the S-phase even in the absence of mitogens
Complete loss of Rb function requires that both alleles are mutated
What is neurofibromatosis?
A familial cancer syndrome due to mutations in the NF1 tumour suppressor
If NF1 function is lost, Ras is constitutively active & cant inactivate
Both alleles need to be mutated to lose NF1 function
NF1 is mutated in a variety of cancer types
What is APC?
A tumour suppressor
What is Beta-catenin?
An oncogene
Significance of Wnt signalling pathway
Mutation of this pathway is an obligate step in colon cancer
When mutated, Cyclin D1 and B-catenin is still on when Wnt is out of range of the paneth cells
SO cells keep proliferating and don’t differentiate = ultimately forms adenoma
What is involved in sustaining proliferative signalling?
Oncogenes = Src, Ras, ß-catenin
TSG = Rb, NF1, APC
TGF-ß signalling
An inhibitory pathway
- TFG-ß signalling acts as a brake on the cell cycle
- Removal of TFG-ß signalling results in the brake being released
- TFG-ß is a tumour suppressor which is mutated in a variety of cancers
